Prescription of anti-influenza drugs in Japan, 2014-2020: A retrospective study using open data from the national claims database.

BACKGROUND: Both physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. Although many countries have national influenza surveillance systems, data on nationwide prescription practices of anti-influenza drugs are lacking. Therefore, we aimed to clarify the status of anti-influenza drug use in Japan by analyzing real-world data. METHODS: This retrospective study analyzed open data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers most claims data from national health insurance. We estimated the annual number of patients prescribed anti-influenza drugs, which drugs they were prescribed, the patients' age and sex distribution, drug costs, and regional disparities for the period 2014-2020. RESULTS: For 2014-2019, an estimated 6.7-13.4 million patients per year were prescribed anti-influenza drugs, with an annual cost of 22.3-48.0 billion JPY (Japanese Yen). In addition, 21.1-32.0 million rapid antigen tests were performed at a cost of 30.1-47.1 billion JPY. In 2017, laninamivir was the most frequently prescribed anti-influenza drug (48%), followed by oseltamivir (36%), while in 2018, the newly introduced baloxavir accounted for 40.8% of prescriptions. After the emergence of COVID-19, the estimated number of patients prescribed anti-influenza drugs in 2020 dropped to just 14,000. In 2018, 37.6% of prescriptions were for patients aged < 20 years compared with 12.2% for those aged ≥ 65 years. Prescriptions for inpatients accounted for 1.1%, and the proportion of prescriptions for inpatients increased with age, with men were more likely than women to be prescribed anti-influenza drugs while hospitalized. CONCLUSIONS: Based on our clarification of how influenza is clinically managed in Japan, future work should evaluate the clinical and economic aspects of proactively prescribing anti-influenza drugs.

Comparison of severe hyponatremia in patients with and without psychiatric diseases: A single-center retrospective study.

Aims: Hyponatremia is a common electrolyte disorder. The severe hyponatremia has a mortality rate of 4%-40%. Psychiatric patients are likely to develop the condition because of polydipsia or the adverse effects of antipsychotics. We investigated the characteristics of patients with and without psychiatric diseases who developed severe hyponatremia. Materials and Methods: We retrospectively investigated cases admitted to our hospital (all departments) between October 2012 and November 2015 with a serum sodium concentration of ≤125 mmol/l on admission. We compared patient characteristics, etiology, and clinical course between psychiatric and nonpsychiatric patients. Results: In total, 123 cases (62 female) were analyzed. Psychiatric disorders were present in 69 cases (56%), including schizophrenia (n = 19), anorexia (n = 16), mood disorders (n = 14), and organic mental disorders (n = 9). The mean patient age was 63 years. The mean serum sodium concentration on admission was 119 mmol/l, and the main causes of hyponatremia were polydipsia (20%), insufficient sodium intake (18%), and syndrome of inappropriate antidiuretic hormone secretion (16%). Compared with the nonpsychiatric group, the psychiatric group was significantly younger (55 vs. 74 years), was more likely to have polydipsia (30% vs. 6%), and had a lower in-hospital mortality (0% vs. 17%). Conclusions: Our study found differences in the clinical picture between psychiatric and nonpsychiatric patients with severe hyponatremia. Clinicians need to monitor serum sodium because the symptoms of hyponatremia can mimic those of psychiatric diseases.

Habitual Hot-Tub Bathing and Cardiovascular Risk Factors in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Several studies suggested that heat therapy, including sauna or hot-tub bathing, was associated with improved glycemia and other risk factors for cardiovascular diseases. This study aimed to assess the influences of the habit of hot-tub bathing on cardiovascular risk factors in patients with type 2 diabetes in a real-world setting. Methods: In this cross-sectional study, we enrolled the patients with type 2 diabetes who regularly visited the outpatient clinic between October 2018 and March 2019. We obtained the information on the habit of hot-tub bathing by using a self-reported questionnaire. The results of anthropometric measurements, blood tests and medications were obtained from the medical charts. We divided the patients into three groups according to the frequency of hot-tub bathing as follows; group 1: ≥ 4 times a week, group 2: < 4 times a week, ≥ 1 time a week, group 3: < 1 time a week. The biomarkers were compared among the groups by one-way analysis of variance. Multiple linear regression analyses were performed to adjust for confounding variables. Results: We enrolled 1,297 patients. There were significant differences in body mass index (group1: 25.5 ± 5.0, group 2: 26.0 ± 5.4, group 3: 26.7 ± 6.0, P = 0.025), diastolic blood pressure (73 ± 12, 75 ± 12, 77 ± 13, P = 0.001) and hemoglobin A1c (7.10 ± 0.97, 7.20 ± 1.11, 7.36 ± 1.67, P = 0.012). Multiple regression analysis revealed that the frequency of hot-tub bathing was a significant determinant of hemoglobin A1c, body mass index and diastolic blood pressure. Conclusions: In this real-world study, habitual hot-tub bathing was associated with slight improvements in glycemia, obesity and diastolic blood pressure, and thus, can be a possible lifestyle intervention in patients with type 2 diabetes.

Hospitalization for urinary tract infections in Japan, 2010-2015: a retrospective study using a national inpatient database.

BACKGROUND: Urinary tract infections (UTI) are common and can have severe consequences. However, there are few recent large-scale studies about them. We aimed to determine the incidence of hospitalization for UTI and to elucidate patient characteristics, clinical practice, and clinical outcomes by drawing on a Japanese nationwide database. METHODS: This was a retrospective observational study using a national database that covers half the acute care inpatients in Japan. Patients aged ≥ 15 years who were hospitalized for UTI were eligible. We did not include patients with lower UTI such as cystitis. We investigated the annual number of patients hospitalized in Japan, those patients' characteristics, and risk factors for in-hospital mortality. RESULTS: We identified 232,396 eligible patients from 31 million records of discharge between April 2010 and March 2015. The average age was 73.5 years and 64.9% of patients were female. The estimated annual number of hospitalizations because of UTI was 106,508. The incidence was 6.8 per 10,000 for men and 12.4 for women. The median medical care cost was 4250 USD. In-hospital mortality was 4.5%. Risk factors of poor survival included male sex, older age, lower bed capacity, non-academic hospital, admission in winter, higher Charlson Comorbidity Index score, low body mass index, coma on admission, ambulance use, disseminated intravascular coagulation, sepsis, renal failure, heart failure, cerebrovascular diseases, pneumonia, malignancies, use of anti-diabetic drugs, and use of corticosteroid or immunosuppressive drugs. CONCLUSIONS: We found that older patients of both sexes accounted for a significant proportion of those hospitalized for UTI. The clinical and economic burden of UTI is considerable.

Metabolic changes of Japanese schizophrenic patients transferred from hospitalization to outpatients.

It is well known that schizophrenic patients have high incidence of metabolic syndrome and life-style related diseases. There are reports that the rates of these diseases are increased more in outpatients than inpatients, but are also reports that the rates are not different between both patient groups. These differences might be related to the length of hospitalization. Hospitalization of Japanese psychiatric patients is about 300 days, much longer than western countries (below 50 days). Therefore, we investigated lipid and glucose metabolism of schizophrenic patients transferred from hospitalization to outpatients at Kohnodai hospital with a mean of 80 days hospitalization period to clarify metabolic characteristics in Japanese patients. Study participants were 144 schizophrenia inpatients and 109 outpatients at Kohnodai Hospital. These 109 outpatients were followed for approximately 2 years, without changes of administrated drugs, and from 144 inpatients. Data from outpatients were obtained at 6 months, 1 year and 2 years after their discharge. Outpatients 2 years after discharge had significantly higher levels of total cholesterol, triglyceride and non-high density lipoprotein (non-HDL) cholesterol than inpatients, accompanied with an increase of body weight. Serum HDL-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels had no significant difference between both groups. These lipids and glucose levels also showed the same tendency in outpatients 0.5 year and 1 year after discharge as those after 2 years. We found that schizophrenic patients in our study appeared to have changes of lipid metabolism 2 years after their discharge, but no significant changes of glucose metabolism, such as FPG and HbA1c.

A cross-sectional study on metabolic similarities and differences between inpatients with schizophrenia and those with mood disorders.

BACKGROUND: One of the main causes of death in psychiatric patients is cardiovascular diseases which are closely related with lifestyle-related diseases. Psychiatric disorders include schizophrenia and mood disorders, whose symptoms and treatment medicines are different, suggesting that they might have different metabolic disorders. Thus, we studied the differences of lifestyle-related diseases between schizophrenia and mood disorders in Japan. METHODS: This cross-sectional study was performed from 2015 to 2017. Study participants were 189 Japanese hospitalized patients (144 schizophrenia group, 45 mood disorders group) in the department of psychiatry at Kohnodai hospital. We examined physical disorders, metabolic status of glucose and lipid, estimated glomerular filtration rate (eGFR) and brain magnetic resonance imaging. We compared these data between schizophrenia and mood disorders groups using analysis of covariance or logistic regression analysis. In comparisons between inpatients with schizophrenia or mood disorders group and the standard, we quoted 'The National Health and Nutrition Survey in Japan 2015' by Ministry of Health, Labor and Welfare as the standard. RESULTS: eGFR and prevalence of smoking were significantly lower in patients with mood disorder group than those with schizophrenia group by adjustment for age. In comparisons between patients with schizophrenia group or mood disorders group and each standard, the ratio of silent brain infarction (SBI) and cerebral infarction were significantly high in both groups. Schizophrenia group showed significantly higher prevalence of diabetes, low high-density lipoprotein (HDL) cholesterolemia, metabolic syndrome and smoking than the standard. Mood disorders group had significantly high prevalence of low HDL-cholesterolemia compared with the standard. Fasting blood glucose and HbA1c were significantly higher in schizophrenia group and female mood disorders group than the standard. Female mood disorders group had significantly decreased eGFR with increased ratio of eGFR < 60 ml/min than the standard. CONCLUSIONS: Participants of both groups had increased ratio of SBI and cerebral infarction, accompanied with glucose and lipid disorders. Compared with schizophrenia group, mood disorders group showed significantly low eGFR and prevalence of smoking.

An Improvement of Cardiovascular Risk Factors by Omega-3 Polyunsaturated Fatty Acids.

An epidemiological survey in the Northwest Greenland reported that the Greenlanders have a lower frequency of acute myocardial infarction and diabetes mellitus. The very low incidence of ischemic heart disease in the Greenlanders was explained by consumption of a diet rich in omega-3 polyunsaturated fatty acids (PUFAs). Possible anti-atherothrombotic effects of omega-3 PUFA include an improvement of lipid metabolism such as a reduction of triglyceride and an increase of high-density lipoprotein-cholesterol (HDL-C), and glucose metabolism, anti-platelet activity, anti-inflammatory effects, an improvement of endothelial function and stabilization of atherosclerotic plaque. The present study reviews an improvement of cardiovascular risk factors such as dyslipidemia and diabetes due to consumption of omega-3 PUFA. A sufficient number of studies suggest that omega-3 PUFA supplementation reduces serum triglyceride and increases HDL-cholesterol. The mechanisms for omega-3 PUFA-mediated improvements of lipid metabolism have been partially elucidated. The studies using experimental animals, part of trials in humans, have shown the beneficial effects of omega-3 PUFA on glucose metabolism and insulin sensitivity. The meta-analysis showed that omega-3 PUFA might prevent development of diabetes in part of population. Further studies should be performed to elucidate the association of omega-3 PUFA supplementation with diabetes, in the future.

Exercise Therapy for Patients With Type 2 Diabetes: A Narrative Review.

To achieve excellent glycemic control in patients with type 2 diabetes, an adequate prescription of exercise therapy is required. The meta-analyses proposed that high-intensity training improves metabolic parameters in patients with pre-diabetes or type 2 diabetes and low physical activity is associated with an increased risk of incident type 2 diabetes. Here, we would introduce literatures about effects of physical activity on mortality, cardiovascular events, and metabolic parameters, to encourage understanding of exercise therapy, and then describe how to prescribe exercise therapy for patients with type 2 diabetes. We also show the usefulness of non-exercise activity thermogenesis for diabetic patients who cannot perform volitional sporting-like exercise because of diabetic complication and/or comorbidity, by presenting results of our previous studies.

Association of handgrip strength with hospitalization, cardiovascular events, and mortality in Japanese patients with type 2 diabetes.

Handgrip strength is useful for the diagnosis of sarcopenia. We examined the associations of handgrip strength with all-cause mortality, cardiovascular events, and hospitalization in patients with type 2 diabetes. From April 2013 to December 2015, we conducted a retrospective cohort study to examine patients with type 2 diabetes whose handgrip strength was measured at our hospital. All patients were followed up until May 2016. A total of 1,282 patients (63.8 ± 13.9 years) were enrolled and followed up for 2.36 ± 0.73 years. During the follow-up period, 20 patients (1.6%) died, 14 (1.1%) experienced cardiovascular events, and 556 (43.4%) were admitted to our hospital for any diseases. Multiple regression analyses revealed that handgrip strength was favorably associated with abdominal obesity and renal function. Moreover, Cox proportional hazard analyses with adjustment for potential confounding variables revealed that handgrip strength was significantly associated with occurrence of CVD events and hospitalization in all subjects. In addition, handgrip strength was significantly associated with mortality and hospitalization in men and with hospitalization in women. Handgrip strength could be a prognostic indicator for health as well as a diagnostic marker of skeletal muscle mass loss in Japanese patients with type 2 diabetes.

Short sleep duration is associated with B-type natriuretic peptide levels and predicts the death of Japanese patients with type 2 diabetes.

OBJECTIVE: To investigate the associations of sleep duration with all-cause mortality, glycemic control, and other clinical parameters of patients with type 2 diabetes. METHODS: From April 2013 to December 2015, we conducted a retrospective cohort study. Study participants were divided into three groups according to their sleep duration. Multiple regression analysis and Cox proportional hazards analysis were performed to assess the independent associations of sleep duration with clinical parameters and all-cause mortality. RESULTS: We enrolled 1233 patients who were then followed for 860 ± 264 days. During the follow-up period, 20 patients (1.6%) died. Sleep duration inversely associated with plasma B-type natriuretic peptide levels (ß = -0.203, p = 0.012) in short (<7 h) sleepers, whereas it was positively associated with hemoglobin A1c levels (ß = 0.156, p = 0.021) in long (≥9 h) sleepers. Moreover, Cox proportional hazard analysis revealed that short sleep duration was a significant predictor of all-cause mortality (hazard ratio = 0.473; confidence interval 0.248-0.905, p = 0.024). CONCLUSION: Short sleep duration may serve as a prognostic indicator of mortality in Japanese patients with type 2 diabetes and may increase cardiovascular stress. Adequate sleep is essential for the management of type 2 diabetes.

Effects of Six Kinds of Sodium-Glucose Cotransporter 2 Inhibitors on Metabolic Parameters, and Summarized Effect and Its Correlations With Baseline Data.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) blocks reabsorption of glucose by inhibiting SGLT2 in kidney, promotes the renal excretion of glucose and improves blood glucose control without requiring insulin secretion. Anti-atherosclerotic effects of SGLT2is have not been fully elucidated until today. METHODS: We retrospectively picked up patients with type 2 diabetes who had been continuously prescribed SGLT2i for 3 months or more between April 2014 and December 2016 by a chart-based analysis, and compared metabolic parameters including coronary risk factors before the SGLT2i treatment with the data at 3 and 6 months after the SGLT2i treatment started. RESULTS: We found 26 patients treated with tofogliflozin, 34 patients with canagliflozin, 27 patients with empagliflozin, 23 patients with ipragliflozin, 68 patients with dapagliflozin and 71 patients with luseogliflozin. Each SGLT2i ameliorated metabolic parameters, in different patterns. SGLT2is reduced body weight, systolic and diastolic blood pressures, plasma glucose, hemoglobin A1c, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, uric acid, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C), and elevated HDL-C; however, they did not affect LDL-cholesterol levels. Change in each metabolic parameter was significantly correlated with each metabolic parameter at baseline. CONCLUSION: The present study demonstrated that SGLT2i ameliorated body weight, blood pressure, liver function, serum lipids and uric acid, in addition to improvement of glucose metabolism in patients with type 2 diabetes.

Hospitalization with hypoglycemia in patients without diabetes mellitus: A retrospective study using a national inpatient database in Japan, 2008-2012.

We aimed to examine prevalence, patient characteristics, etiology, and clinical outcomes of hospitalized patients who had hypoglycemia without a diagnosis of diabetes mellitus, using a Japanese nationwide database.This was a retrospective observational study using a national database of acute-care inpatients in Japan. Nondiabetic patients aged ≥15 years who were hospitalized for hypoglycemia were eligible. We estimated the annual numbers of hospitalized cases in Japan. We also investigated the patient characteristics, and risk factors of in-hospital mortality.We identified 8684 eligible patients out of 22.7 million discharge records between July 2008 and March 2013. The average age was 70.0 years and the average body mass index (BMI) was 19.9 kg/m. Most frequently recorded underlying diseases were malignancies, cerebrovascular diseases, pneumonia, renal failure, and heart failure. The estimated annual numbers of hospitalizations because of hypoglycemia in nondiabetic patients were 5000 to 7000. In-hospital mortality was 14.9%, and predictive factors for poor survival included older age, community hospital, low BMI, coma at admission, urgent admission, renal failure, heart failure, pneumonia, sepsis, chronic liver diseases, and malignancies.Patients without diabetes mellitus but with hypoglycemia had multiple comorbidities and high in-hospital mortality. Clinicians should carefully investigate the etiology of hypoglycemia in nondiabetic patients, and treat the underlying diseases.

Development of diabetes mellitus associated with quetiapine: A case series.

We aimed to describe the characteristics and clinical course of patients who developed diabetes associated with the use of quetiapine.This study included patients who received quetiapine for over a month between April 2008 and November 2013, and were diagnosed as having new-onset diabetes after initiation of quetiapine. We excluded patients who developed diabetes more than 1 year after discontinuation of quetiapine. We identified new-onset diabetes by hemoglobin A1c or prescriptions of antidiabetic drugs.Among 1688 patients who received quetiapine, hemoglobin A1c had been measured in 595 (35.2%) patients at least once during the observation period, and 33 (2.0%) patients had received hypoglycemic drugs. Eighteen (1.1%) patients were considered to have developed new-onset diabetes associated with quetiapine after a median of 1.6 years following initiation of quetiapine. Median (interquartile range) age was 54.5 (29.8) years, 8 patients were male, and median (interquartile range) duration of mental illness was 15.3 (13.8) years. Median hemoglobin A1c and body mass index (BMI) were 7.1 (1.4) % and 28.4 (7.0) kg/m, respectively. Seventeen patients had dyslipidemia when diabetes was discovered. All of these discontinued quetiapine within 3 months after the diagnosis of diabetes, and the diabetes in 4 patients had ameliorated without hypoglycemic drugs. Of 13 patients who had received either oral hypoglycemic drugs or insulin, 2 patients achieved well-controlled hemoglobin A1c without hypoglycemic drugs, and 10 patients had hemoglobin A1c 5.0% to 7.7% with the continued use of hypoglycemic drugs.We demonstrated that almost all patients who developed quetiapine-associated diabetes had dyslipidemia and increased BMI. There was no life-threatening hyperglycemia and diabetes was ameliorated just by discontinuation of quetiapine in several patients. The monitoring of metabolic parameters during antipsychotic treatment is important to diagnose and treat diabetes earlier.

The Influences of Withdrawal and Daily Dose Reduction of Pioglitazone on Metabolic Parameters in Patients With Type 2 Diabetes: A Retrospective Longitudinal Observational Study.

BACKGROUND: The aim of the study was to understand the influences of withdrawal or dose reduction of pioglitazone in patients with type 2 diabetes. METHODS: We retrospectively picked up patients who had undergone withdrawal or daily dose reduction of pioglitazone after a continuous prescription for 3 months or longer between January 2010 and March 2014. We compared the data before the withdrawal or dose reduction of pioglitazone with the data at 3 or 6 months after those by a chart-based analysis. RESULTS: Among 713 patients taking pioglitazone at least once during the studied period, 20 patients had undergone withdrawal of pioglitazone (group A) and 51 patients had undergone daily dose reduction (group B). The mean pioglitazone dose at baseline was 23 mg in subjects of group A, and 30 mg in group B. The number of subjects who had taken high-dose metformin (≥ 1,000 mg) and dipeptidyl peptidase-4 (DPP-4) inhibitors increased after the withdrawal or dose reduction of pioglitazone in both groups. Although no significant change was observed in plasma glucose and HbA1c levels, body weight significantly decreased at 3 and 6 months after the dose reduction in group B. The same tendency was observed in group A. Serum high-density lipoprotein-cholesterol (HDL-C) levels significantly decreased at 3 and 6 months after the withdrawal in group A. The serum alanine aminotransferase levels significantly increased 3 months after the withdrawal in group A. CONCLUSIONS: Present study demonstrated that the withdrawal of pioglitazone exacerbated serum HDL-C and liver function in patients with type 2 diabetes, although glycemic control could be maintained by using high-dose metformin or DPP-4 inhibitors.

Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Metabolic Parameters in Patients With Type 2 Diabetes: A Chart-Based Analysis.

BACKGROUND: Effects of the new class of anti-diabetic drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, on metabolic parameters in patients with type 2 diabetes remain largely unknown. METHODS: We retrospectively picked up patients who had been continuously prescribed SGLT2 inhibitors for 1 month or more between April 2014 and November 2015 by a chart-based analysis, and compared the data before the SGLT2 inhibitor treatment with the data at 1, 2, 3 and 6 months after the SGLLT2 inhibitor treatment started. RESULTS: Fifty patients were eligible for the analyses in our study. The HbA1c levels as well as body weight significantly decreased at 1, 2, 3 and 6 months after the start of SGLT2 inhibitors. Systolic blood pressure tended to decrease only at 1 and 2 months, but there was no change at 3 and 6 months. No significant change was observed in serum high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and non-HDL-C levels. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels significantly decreased at 3 and 6 months after the prescription. The hematocrit levels significantly increased at 1, 2, 3 and 6 months, and the estimated glomerular filtration rate (eGFR) levels significantly decreased at 1 month after the start of SGLT2 inhibitors. A significant correlation between reductions in HbA1c levels and HbA1c levels at baseline was observed at 1, 3 and 6 months. The decreases in serum ALT levels were also significantly correlated with the baseline ALT levels at 3 and 6 months. CONCLUSION: Present study demonstrated that SGLT2 inhibitors significantly reduced HbA1c and body weight and improved liver functions, whereas no significant change was observed in serum lipid profiles.

The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an established independent risk factor for hepatocellular carcinoma (HCC). T2DM is associated with non-alcoholic steatohepatitis (NASH), which is a major cause of non-HBV and non-HCV-related HCC; nevertheless, it has been difficult to identify those patients with T2DM who have a high risk of developing HCC. The aim of this study was to identify genetic determinants that predispose T2DM patients to HCC by genotyping T2DM susceptibility loci and PNPLA3. METHODS: We recruited 389 patients with T2DM who satisfied the following three criteria: negative for HBs-Ag and anti-HCV Ab, alcohol intake <60 g/day, and history of T2DM >10 years. These patients were divided into two groups: T2DM patients with HCC (DM-HCC, n = 59) or those without HCC (DM-non-HCC, n = 330). We genotyped 51 single-nucleotide polymorphisms (SNPs) previously reported as T2DM or NASH susceptibility loci (PNPLA3) compared between the DM-HCC and DM-non-HCC groups with regard to allele frequencies at each SNP. RESULTS: The SNP rs738409 located in PNPLA3 was the greatest risk factor associated with HCC. The frequency of the PNPLA3 G allele was significantly higher among DM-HCC individuals than DM-non-HCC individuals (OR 2.53, p = 1.05 × 10(-5)). Among individuals homozygous for the PNPLA3 G allele (n = 115), the frequency of the JAZF1 rs864745 G allele was significantly higher among DM-HCC individuals than DM-non-HCC individuals (OR 3.44, p = 0.0002). CONCLUSIONS: PNPLA3 and JAZF1 were associated with non-HBV and non-HCV-related HCC development among Japanese patients with T2DM.

Sodium-Glucose Cotransporter 2 Inhibitors: Possible Anti-Atherosclerotic Effects Beyond Glucose Lowering.

The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We searched by using Pubmed, and found 770 published articles about SGLT-2 inhibitors. Among 10 kinds of SGLT-2 inhibitors, the number of published articles about dapagliflozin was the greatest among SGLT-2 inhibitors. Since SGLT-2 inhibitors have similar chemical structures, we concentrated on the published articles about dapagliflozin. SGLT-2 inhibitors are proved to be significantly associated with weight loss and reduction of blood pressure by a relatively large number of studies. The studies investigating effects of dapagliflozin on visceral fat, insulin sensitivity, serum lipids, inflammation and adipocytokines are very limited. An influence of increase in glucagon secretion by SGLT-2 inhibitors on metabolic risk factors remains unknown.

Associations between lower extremity muscle mass and metabolic parameters related to obesity in Japanese obese patients with type 2 diabetes.

Background. Age-related loss of muscle mass (sarcopenia) increases the incidence of obesity in the elderly by reducing physical activity. This sarcopenic obesity may become self-perpetuating, increasing the risks for metabolic syndrome, disability, and mortality. We investigated the associations of two sarcopenic indices, the ratio of lower extremity muscle mass to body weight (L/W ratio) and the ratio of lower extremity muscle mass to upper extremity muscle mass (L/U ratio), with metabolic parameters related to obesity in patients with type 2 diabetes and obesity. Methods. Of 148 inpatients with type 2 diabetes treated between October 2013 and April 2014, we recruited 26 with obesity but no physical disability. Daily physical activity was measured by a triaxial accelerometer during a period of hospitalization, and which was also evaluated by our previously reported non-exercise activity thermogenesis questionnaire. We measured body composition by bioelectrical impedance and investigated the correlations of L/W and L/U ratios with body weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), visceral fat area, subcutaneous fat area, serum lipid profile, and daily physical activity. Results. The L/W ratio was significantly and negatively correlated with BMI, WC, WHR, body fat mass, body fat percentage, subcutaneous fat area, and serum free fatty acid concentration, was positively correlated with daily physical activity: the locomotive non-exercise activity thermogenesis score, but was not correlated with visceral fat area. The L/U ratio was significantly and positively correlated with serum high-density lipoprotein cholesterol. Conclusions. High L/W and L/U ratios, indicative of relatively preserved lower extremity muscle mass, were predictive of improved metabolic parameters related to obesity. Preserved muscle fitness in obesity, especially of the lower extremities, may prevent sarcopenic obesity and lower associated risks for metabolic syndrome and early mortality.

Associations of Low-Intensity Resistance Training with Body Composition and Lipid Profile in Obese Patients with Type 2 Diabetes.

Resistance training to increase muscle mass and functional capacity is an integral part of diet and exercise programs for the management of obesity and type 2 diabetes. Low-intensity resistance training with slow movement and tonic force generation (LST) may be a practical and safe regimen for elderly obese individuals but the health benefits are uncertain. This study investigated the effects of LST on body composition and metabolic parameters in obese patients with type 2 diabetes. Twenty-six obese patients with type 2 diabetes engaged in LST training during hospitalization and were advised to maintain this regimen for 12 weeks after discharge. We compared lipid profile, arterial stiffness, and body composition before and after LST training. After 12 weeks of LST training, the ratio of lower extremity muscle mass to body weight increased significantly (0.176 ± 0.028 to 0.184 ± 0.023, mean ± SD), while body fat mass and body fat percentage decreased significantly (36.2 ± 10.9 kg to 34.3 ± 9.4 kg and 41.2 ± 8.6% to 40.1 ± 7.7%, respectively). Moreover, high-density lipoprotein cholesterol was significantly increased (42.2 ± 14 mg/dl to 46.3 ± 12.4 mg/dl) and both free fatty acids and lipoprotein(a) were decreased (665.2 ± 212.1 µEq/l to 525.4 ± 231.3 µEq/l and 15.4 ± 18 mg/dl to 13.8 ± 18 mg/dl, respectively). No significant change was observed in arterial stiffness. Although this study was a non-controlled investigation and some confounding factors including dietary intake, medication and compliance with training might affect the study result, a brief (12-week) LST training program may be a safe and effective strategy for the management of obesity and type 2 diabetes.